03 030708e caffeine anhydrous

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Pharma Ingredients& Services

Caffeine AnhydrousTechnical InformationJanuary 2010

Supersedes issue dated October 2009

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= Registered trademark of BASF group Ph. Eur., USP, JP


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1. Medical indication Caffeine is a methylxanthine (like theophylline or theobromine), a natural substancederived from the purine found in various plant families worldwide. Well-knownexamples of plants in which Caffeine is found include coffea arabica (coffee), theasinensis (black tea), ilex paraguayensis (mate) and cola vera (cola nuts). These have been used as stimulants since ancient times.

In terms of pharmacology and therapy, methylxanthines belong to the group ofpsychoanaleptics. Methylxanthines affect the central nervous system, the cardio-

vascular system, the skin, the kidneys and also act as phosphor diesterase inhibitors.

Caffeine is mostly used in combination with analgesics and antihistamines, but itis also used in the treatment of apnoea in newborns, in skin care products and inthe food and beverage industry.

Pharmacology Among the methylxanthines, Caffeine has the most distinctive central effect. Itprimarily acts on the cerebral cortex and stimulates psychic and sensory functions.Caffeine increases mental receptivity and efficiency and reduces fatigue. Only highdoses stimulate the autonomic nervous system.

The effects of Caffeine on the cardiovascular system, especially in acute circulatoryfailure, are based on the stimulation of vasomotor centres and, in part, on the excitationof the myocardium.

Various peripheral vessels in the kidneys and other areas innervated by the splanchnicnerve as well as the coronaries are dilated by Caffeine. However, blood pressureis generally not affected.

The tone of the cerebral vessels is raised and the cerebrospinal pressure reduced.Caffeines effect on vascular headaches is attributed to this factor.

At relatively high doses, Caffeine and theophylline inhibit phosphodiesterase, anenzyme that degrades cyclic adenosine monophosphate (cAMP) to the inactiveadenosine monophosphate. This leads to an increase in cAMP concentrations,affects smooth muscle spasmolysis and promotes glycogenolysis and lipolysis.The lipolytic effect is seen in increasing plasma concentrations of free fatty acidsafter oral ingestion of Caffeine. The high concentration of cAMP activates a specific

enzyme that hydrolyses the triglycerides to fatty acids and glycerol.

This lipolytic effect can also be used in the cosmetics industry in the managementof cellulites.

Other pharmacological properties of caffeine, such as suppression of fatigue byincreasing the amount of oxygen in the CNS cells, are explained by its competitiveinhibition of adenosine receptors. By promoting the release of noradrenaline,adrenaline and especially dopamine, Caffeine also has a positive effect in thetreatment or prevention of Parkinsons disease.

Pharmacokinetics Caffeine is almost completely absorbed. Peak plasma levels are reached within30 minutes. The apparent distribution volume is between 0.35 1.1 l/kg.

The substance is excreted with the urine. Its biological half-life is about 3 5 hours.Smokers eliminate Caffeine twice as fast as non-smokers because of enzymeinduction.

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2. Chemical Information

Name Caffeine

Trade name Caffeine Anhydrous

Chemical name 1,3,7-Trimethylxanthine

CAS-No. 58-08-2

EINECS-No. 200-362-1Structural formula

Empirical formula C8H

10N

4O

2

Molecular weight 194.19 g/mol



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3. Grades PRD-No. Particle size

30057897 Not less than 95%pass 0.300 mm sieve (No. 50)

Caffeine Anhydrous Powder50 kg1 kg (sample)0.05 kg (sample)


Caffeine Anhydrous FinePowder

50 kg0.05 kg (sample)


Not more than 29%pass 0.150 mm sieve (No. 100)

10 29%pass 0.075 mm sieve (No. 200)

Caffeine Anhydrous Granular0.07/0.5

50 kg0.5 kg (sample)0.05 kg (sample)




100 kg50 kg1 kg (sample)0.05 kg (sample)







Not more than 30%

pass 0.500 mm sieve (No. 35)Not more than 5%pass 0.063 mm sieve (No. 230)



Retest period See separate documentation: Q&R PI (not for regulatory purposes) available atBASFs WorldAccount: https://worldaccount.basf.com (registered access).

4. Physical and chemical

properties

Solubility: Water: sparingly solubleEthanol: slightly solubleEther: slightly soluble

5. Regulatory status Caffeine Anhydrous meets current Ph. Eur., USP, and JP monographs.EDMF, US-DMF, JDMF, and CEP (CoS) are available upon request and whennecessary.

6. Specifications See separate document: Standard Specification (not for regulatory purposes)available via BASFs WorldAccount: https://worldaccount.basf.com (registeredaccess).



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7. Particle characterization The following data strongly depend on the operator and method employed andmay vary from lab to lab.

7.1 Caffeine Anhydrous Powder

Particle size specification Not less than 95% pass 0.300 mm sieve (No. 50)

Volume Loose bulk volume approx. 2.3 ml/g

Bulk volume approx. 2.1 ml/g

Tapped volume approx. 1.5 ml/g

SEM photographs



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7.2 Caffeine Anhydrous Fine Powder

Particle size specification Not less than 97% pass 0.150 mm sieve (No. 100)




SEM photographs



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7.3 Caffeine Anhydrous Granulated0.07/0.5

Particle size specification Not less than 100% pass 0.500 mm sieve (No. 35)Not more than 29% pass 0.150 mm sieve (No. 100)10 29% pass 0.075 mm sieve (No. 200)


Bulk volume approx. 1.6 ml/gTapped volume approx. 1.4 ml/g

SEM photographs



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Particle size specification Not less than 97% pass 0.500 mm sieve (No. 35)Not more than 10% pass 0.212 mm sieve (No. 70)

Volume Bulk volume approx. 1.6 ml/g


SEM photographs



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Particle size specification Not less than 90% pass 0.710 mm sieve (No. 25)Not more than 10% pass 0.212 mm sieve (No. 70)




SEM photographs



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Particle size specification Not less than 95% pass 1.005 mm sieve (No. 30)Not more than 60% pass 0.600 mm sieve (No. 30)Not more than 30% pass 0.500 mm sieve (No. 35)Not more than 5% pass 0.063 mm sieve (No. 230)

Volume Bulk volume approx. 1.6 ml/gTapped volume approx. 1.5 ml/g

SEM photographs



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8. Formulations Besides its use in pharmaceutical and skin care products, the largest amount ofCaffeine is used for soft drinks such as colas and energy drinks.

Pharmaceutical applications In the pharmaceutical industry, and especially in the United States, Caffeine is oftensold in pill form intended to keep the taker awake. However, Caffeine is mostly usedin combination products with painkillers such as paracetamol, acetyl salicylic acidor ibuprofen. Caffeine has an additive effect in combination with these active

substances.

Caffeine tablets Caffeine, fine powder 50 mg

Avicel PH 200 40 mg

KollidonVA 64 4 mg

Kollidon CL 5 mg

Magnesium stearate 0.5 mg

Aerosol 200 0.5 mg

Mix all ingredients and compress in 6 mm round tablets.

Compression force 2.5 kN

Hardness 92 NDisintegration within 1 min

Dissolution more than 80% after 10 min

General information for tableting: small grades result in higher hardness at lowcompression forces.

In most cases, caffeine may be added as a dry powder (without prior granulation)to painkiller formulations, and compressed into tablets.

Cosmetic applications Caffeine is often used in skin care products such as creams or gels. When appliedon the skin, there is a widening of the small blood vessels in the skin. As a result,the skin can appear fresher and there may be a reduction of small wrinkles.

High content caffeine gel Caffeine, powder 200 7.0%

Carbopol 971 0.5%

Deionized water 64.5%

Ethanol 28.0%

Caffeine is dissolved in a water/ethanol mixture at 50 C. After cooling to about20 C, carbopol is added and dissolved and the pH value adjusted to 6.5 6.8 using0.1 mol NaOH. Tetraethylene diamine may be used instead of NaOH. The resultinggel takes several hours to form.

Note This document, or any answers or information provided herein by BASF, does not

constitute a legally binding obligation of BASF. While the descriptions, designs, dataand information contained herein are presented in good faith and believed to beaccurate, it is provided for your guidance only. Because many factors may affectprocessing or application/use, we recommend that you make tests to determinethe suitability of a product for your particular purpose prior to use. It does not relieveour customers from the obligation to perform a full inspection of the products upondelivery or any other obligation. NO WARRANTIES OF ANY KIND, EITHER EXPRESSOR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESSFOR A PARTICULAR PURPOSE, ARE MADE REGARDING PRODUCTS DESCRIBEDOR DESIGNS, DATA OR INFORMATION SET FORTH, OR THAT THE PRODUCTS,DESIGNS, DATA OR INFORMATION MAY BE USED WITHOUT INFRINGING THEINTELLECTUAL PROPERTY RIGHTS OF OTHERS. IN NO CASE SHALL THEDESCRIPTIONS, INFORMATION, DATA OR DESIGNS PROVIDED BE CONSIDEREDA PART OF OUR TERMS AND CONDITIONS OF SALE.

January 2010


03 030708e caffeine anhydrous

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